In spite of anatomic and physiologic studies showing a fundamental role for central vestibular structures in the control of posture and movement, little is known abut the neurochemical basis of vestibular function. Acetylcholine may play a transmitter role in vestibular systems as shown by a variety of anatomic, physiologic, biochemical and clinical evidence. I have begun studies of central vestibular cholinergic systems by making lesions of structures with afferent or efferent connections with the vestibular nuclear complex (VNC) and then measuring a cholinergic marker, choline acetyltransferase (CAT), in VNC. Labyrinthectomy, thoracic (T3) cordotomy and vestibular commissurotomy do not affect VNC CAT activity. However, cerebellectomy and injection of kainate into VNC decrease it. I plan to study further a possible vestibulo-cerebellar cholinergic relationship by doing additional selective lesion experiments. For example, I will lesion VNC and measure archicerebellum CAT activity. I will also lesion fastigial nucleus and archicerebellum and measure VNC CAT activity. In addition to this approach, which uses a biochemical marker to study vestibular cholinergic anatomy, I will use a recently developed autoradiographic technique which employs specific retrograde transport of 3H-choline to identify cholinergic neurons. I will use this technique to study vestibulo-cerebellar cholinergic anatomy, and to search for possible reticular and interstitial nucleus cholinergic projections to VNC. Results from these studies are likely to enhance our understanding of the biochemical basis of clinical disorders of movement and posture. Clinical and pathological data suggest involvement of the vestibular nuclei in Parkinson Disease and other parkinsonian syndromes. In addition, we have shown that vestibular mechanisms are involved in a proposed animal model of torsion dystonia.